Discovery Shows Rapid Evolution of Bacterial Genomes Over the Course of a Single Chronic Infection

Researchers from the Center for Genomic Sciences at Allegheny General Hospital (AGH) in Pittsburgh have made a landmark discovery about the evolutionary nature of bacteria in the setting of chronic infectious disease. Reporting today in the journal PLos Pathogens, the AGH team documents for the first time that bacteria engage in a process called horizontal gene transfer to evolve rapidly during the course of a single infection.

The result is a group of highly-related bacterial strains that are changing genetically so fast that it is likely nearly impossible for the host's immune system to effectively track and eradicate it, says Garth Ehrlich, PhD, scientific director of the Center for Genomic Sciences and the paper's senior author.

"Much like we see with other successful pathogens, such as viruses and certain parasitic organisms, which are designed to mutate and confuse the immune system, bacteria which cause the vast majority of chronic infectious disease in the United States appear to be using a similar tactic. And they are doing so through a dynamic, real-time process of altering their genetic code that until now has not been understood and which is counter to conventional wisdom about the typical pace of species evolution," Ehrlich says.

Using advanced high throughput bacterial DNA sequencing, Ehrlich and his colleagues investigated the tempo and relevance of horizontal gene transfer among nasopharyngeal strains of Streptococcus pneumoniae recovered from a child with chronic respiratory and middle ear infections. Specimens were collected during the child's clinic visits over a seven-month period.

"We identified extensive gene transfer among multiple infecting strains of the bacteria. Comparing the original strain that started the infection with strains sequenced at its end, approximately 7.5 percent of the entire genome had changed. In just a seven-month period of time, we documented a remarkable ongoing evolution of this species that appears to be precisely orchestrated to confound the host's immune surveillance," Ehrlich says.

The immune system works in a similar fashion, Ehrlich says, by continuously realigning the genomes of white blood cells so they can recognize and destroy foreign pathogens.

"It is essentially a genomic chess match where bacteria, through horizontal gene transfer, are always staying one step ahead," Ehrlich adds. "Once we have verified that horizontal gene transfer is indeed a common occurrence in chronic bacterial infections, and we expect that to be the case, it opens the door to a realm of promising new directions in the study and treatment of these diseases," he said.